Therapeutic composition and methods

Abstract

In exemplary embodiments, the disclosure provides a Colesevelam Colon Specific Drug Delivery System for use in treatment of, for example, cholestasis and/or cholestatic pruritus.

What is claimed is: 
     
       1. An oral drug delivery system comprising:
 a) a core comprising:
 a therapeutically effective amount of at least one active agent present in an amount of from about 50% to about 64% w/w of the core, wherein the at least one active agent is selected from the group consisting of colesevelam, pharmaceutically acceptable salts thereof, and combinations thereof, and 
 a drug release controlling component capable of providing release of the at least one active agent primarily in a region of a patient selected from the group consisting of a lower gastrointestinal tract, a large intestine, a jejunum, a ileum, a cecum, a colon, a rectum, and combinations thereof, 
 wherein the drug release controlling component comprises low viscosity hydroxypropyl methyl cellulose (HPMC) and high viscosity HPMC, and 
 comprises at least one erodible matrix material selected from the group consisting of hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), hydroxypropyl methyl cellulose acetate trimellitate (HPMCAT), ethylhydroxy ethylcellulose (EHEC), and combinations thereof, wherein said at least one erodible matrix material is present in a concentration of about 5% to about 15% w/w of the core; 
 
 b) a barrier coating encasing the core, wherein said barrier coating comprises HPMC, and 
 c) an enteric coating on the barrier coating comprising hypromellose acetate succinate, and further comprising a plasticizer, 
 wherein after ingestion by the patient the at least one active agent is released primarily in the region selected from the group consisting of the lower gastrointestinal tract, the large intestine, the jejunum, the ileum, the cecum, the colon, the rectum, and combinations thereof. 
 
     
     
       2. The system of  claim 1 , wherein the at least one active agent is present in an amount selected from the group consisting of about 250 mg, about 500 mg, about 625 mg, and about 650 mg. 
     
     
       3. The system of  claim 1 , wherein the at least one active agent is present in an amount of about 250 to about 650 mg. 
     
     
       4. The system of  claim 1 , wherein the at least one active agent is present in an amount of about 63.13% w/w of the core. 
     
     
       5. The system of  claim 1 , wherein the oral drug delivery system releases the at least one active agent primarily in the lower gastrointestinal tract. 
     
     
       6. The system of  claim 1 , wherein about 80% to about 100% w/w of the at least one active agent is released in the lower gastrointestinal tract. 
     
     
       7. The system of  claim 1 , wherein about 100% w/w of the at least one active agent is released in the lower gastrointestinal tract. 
     
     
       8. The system of  claim 1 , wherein the oral drug delivery system releases the at least one active agent primarily in the large intestine. 
     
     
       9. The system of  claim 1 , wherein about 80% to about 100% w/w of the at least one active agent is released in the large intestine. 
     
     
       10. The system of  claim 1 , wherein about 100% w/w of the at least one active agent is released in the large intestine. 
     
     
       11. The system of  claim 1 , wherein the oral drug delivery system releases the at least one active agent primarily in the colon. 
     
     
       12. The system of  claim 1 , wherein about 80% to about 100% w/w of the at least one active agent is released in the colon. 
     
     
       13. The system of  claim 1 , wherein about 100% w/w of the at least one active agent is released in the colon. 
     
     
       14. The system of  claim 1 , wherein the at least one erodible matrix material is present in a concentration of about 8% to about 13% w/w of the core. 
     
     
       15. The system of  claim 1 , wherein the at least one erodible matrix material is present in a concentration of about 12.12% w/w of the core. 
     
     
       16. The system of  claim 1 , wherein the core further comprises at least one excipient selected from the group consisting of: diluent, binding agent, lubricant, disintegrant, stabilizer, and combinations thereof. 
     
     
       17. The system of  claim 1 , wherein the core further comprises a disintegrant, wherein the disintegrant comprises colloidal silicon dioxide, in an amount of from about 0.1% to about 4% w/w of the core. 
     
     
       18. The system of  claim 1 , wherein the core further comprises a lubricant, wherein the lubricant comprises magnesium stearate, in an amount of from about 0.1% to about 4% w/w of the core. 
     
     
       19. The system of  claim 1 , wherein the enteric coating allows the at least one active agent to pass through a stomach substantially intact and subsequently disintegrate primarily in the large intestine of the patient. 
     
     
       20. The system of  claim 1 , wherein the plasticizer is present in a concentration of about 0.5% to about 2% w/w of the enteric coating. 
     
     
       21. The system of  claim 1 , wherein the plasticizer is present in a concentration of about 0.75% to about 1% w/w of the enteric coating. 
     
     
       22. The system of  claim 1 , wherein the plasticizer is present in a concentration of about 0.87% w/w of the enteric coating. 
     
     
       23. The system of  claim 1 , wherein the plasticizer is selected from the group consisting of dibutyl sebacate, diethyl phthalate, triethyl citrate, tributyl citrate, triacetin, acetylated monoglycerides, diacylated monoglyceride, phthalate esters, castor oil, and combinations thereof. 
     
     
       24. The system of  claim 1 , wherein the plasticizer is triethyl citrate.